OVERVIEW: What every practitioner needs to know

Are you sure your patient has a snake bite? What are the typical findings for this disease?

Pit viper venom can affect nearly every system of the body, but it is most notable for local tissue effects as well as hematologic abnormalities. Local signs and symptoms include acute pain at the site, edema, erythema, and often ecchymoses. These changes are most often seen within one hour of envenomation. Hematologic effects include coagulopathy, thrombocytopenia, and hypofibrinogenemia which has also been referred to as venom-induced consumption coagulopathy. Additional signs and symptoms can include hemorrhagic blebs or bullae at the site, tissue necrosis, nausea, vomiting, diaphoresis, hypovolemic shock, paresthesia, metallic taste, altered mental status, seizures, lymphangitis, rhabdomyolysis, and respiratory failure.

Elapidae (Coral snakes)

Coral snake bites elicit predominantly neurotoxic effects with very little local injury. These effects can occur as late as 12-24 hours after the envenomation. Other signs and symptoms include nausea, vomiting, respiratory failure secondary to muscle weakness, hypersalivation, ptosis, dysarthria, dysphagia, altered mental status (lethargy or euphoria), fasciculations, and seizures.

* Of note, the Mojave rattlesnake venom toxin is neurotoxic; thus, signs and symptoms of envenomation may resemble those described above for coral snake envenomation.

What other disease/condition shares some of these symptoms?

In considering the diagnosis of a venomous snake bite, it is important to exclude bites by other animals, for example, spider bites and nonvenomous snake bites. It is also important to rule out other causes of puncture wounds. Identification of the snake as well as clinical manifestations are the mainstays of diagnosis. However, snakes maintain a bite reflex even after death, so caution should be taken with regard to any attempt to capture the snake for identification.

Nonvenomous snakes typically have a round head, no heat-sensing pit, round pupils, and a double row of plates caudal to the anal plate. In contrast, venomous snakes have triangular heads, elliptical eyes, and a heat-sensing pit between each eye and nostril. They are also known to have a single row of plates along the tail, caudal to the anal plate.

There exist numerous species of Rattlesnakes with differing color markings; however, their characteristic trait is that of the "rattle." The rattle is composed of segments that vibrate against each other. The initial segment is called the prebutton and is made of keratin. Each skin shedding by the snake adds segments (Figure 1). Rattlesnakes may strike without warning.

Figure 1.

Eastern Diamondback Rattlesnake

Copperheads are typically tan to pinkish in color, with copper-colored heads and characteristic hourglass-like patterned bands across their body (Figure 2). Envenomation by a copperhead snake is often less toxic compared with that of rattlesnakes and cottonmouths, and does not always require antivenom.

Figure 2.

Copperhead

Cottonmouths or water moccasins are dark green to black in color with a white gullet (Figure 3 and Figure 4). They are semiaquatic and aggressive.

Figure 3.

Figure 4.

Water moccasin

Lastly, coral snakes have a round head and black, yellow, and red banding (Figure 5). Their head color is black compared to the nonvenomous scarlet king snake, which mimics the coral snake coloring. A common rhyme is red on yellow kill a fellow, red on black friend of Jack.

Figure 5.

Eastern coral snake Source: Norman.benton

What caused this disease to develop at this time?

N/A

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Crotalinae:

Complete blood count (evaluate hematocrit due to risk for hemolysis and platelets secondary to risk for thrombocytopenia)

Would imaging studies be helpful? If so, which ones?

N/A

Confirming the diagnosis

Pit viper envenomation is typically described as minimal, moderate, or severe. Mild envenomation consists of purely local effects without systemic signs or symptoms or abnormal laboratory values. Moderate envenomation reveals local effects that do not include the entire extremity, mild systemic signs or symptoms, or mild laboratory abnormalities. Severe envenomation includes progression of local effects (swelling, erythema, edema, and ecchymoses) of the entire extremity or concern for airway compromise, life-threatening systemic signs or symptoms, or significantly abnormal coagulation studies.

Of note, the severity of envenomation should be based on the most severe sign, symptom, or laboratory value. Evidence of envenomation indicates the use of antivenom with the exception of mild envenomation by a known copperhead snake bite. A known mild envenomation by a copperhead snake may be treated with supportive care, close observation, and appropriate laboratory evaluation.

Interestingly, 20-30% of pit viper bites have been described as "dry" bites without any envenomation. As many as 50-60% of coral snake bites may be considered "dry" bites. This is likely due to the mechanism by which coral snakes inject their venom. Unlike the pit vipers with long, retractable fangs, the coral snake has short fixed fangs. They inject their venom by latching onto the victim and gnawing at the site of latch.

Coral snake envenomation may not have local injury, and victims are at risk for neurotoxicity up to 12-24 hours post envenomation. Thus, serial neurologic exams should be performed for at least 12 hours. If available, antivenom should be given to anyone with confirmed coral snake envenomation or neurologic symptoms following a suspected Texas or Eastern coral snake bite. However, once neurotoxicity is evident, it may not be possible to reverse the effects, and supportive care with endotracheal intubation and mechanical ventilation may be necessary.

The physical exam should focus particularly on the cardiovascular, pulmonary, and neurologic systems.

If you are able to confirm that the patient has a snake bite, what treatment should be initiated?

The most immediate action of care should be to remove the victim from the snake's vicinity and transfer the patient to the nearest medical facility. Immobilize the affected limb at or below the level of the heart. As always, early evaluation and resuscitation should maintain pediatric basic life support of circulation, breathing, and airway. For North American snake envenomation, tourniquets, suction, and cryotherapy are not indicated. Pressure immobilization for snake venom with neurotoxic effects alone, such as coral snakes, is an area of debate. Further, alcohol or drugs that could alter the victim's mental status are not advised.

A helpful technique is to mark with permanent marker the initial area of erythema, edema, and ecchymoses as well as subsequent progression. This can also be enhanced by taking serial circumferential measurements proximal and distal to the bite site.

Tetanus prophylaxis should be guided by the patient's immunization history and current guidelines. Wound infection is rare, and antibiotics are not generally indicated unless there is clear evidence of bacterial infection.

Consultation with a medical expert is encouraged prior to initiation of antivenom therapy. A medical toxicologist is available through the regional Poison Control Center, 1-800-222-1222 FREE. Any patient receiving antivenom should be admitted to the ER or ICU due to the risk for anaphylaxis.

Pit viper antivenom is Crotalidae Polyvalent Immune Fab (Ovine); (CroFab, Protherics Inc, Nashville, Tenn). It is most effective if given within the first 4-6 hours after envenomation. The initial dose is 4-6 vials, with re-evaluation (clinical and coagulation studies) one hour after administration. If the patient has not responded (worsening coagulopathy or clinical signs and symptoms or has had no improvement), then repeat dosing of 4-6 vials is indicated. Once progression of local injury, systemic effects and coagulopathy has ceased, then the patient should be given maintenance dosing of 2 vials every six hours for three doses.

Currently, there is no manufacturing of North American Coral Snake Antivenom. The FDA has granted an extension of the available stock, (lot 4030024) until April 30, 2016, and will consider further expiration date extensions as stability data of the product becomes available. If Antivenin (North American Coral Snake Antivenom) is indicated but unavailable at your local institution, then the regional Poison Control Center or Pfizer Inc. should be contacted for further assistance. If available, the initial dose for North American Coral Snake Antivenom is approximately 5 vials. If symptoms develop or signs of weakness progress, then 10-15 additional vials may be indicated.

Antivenom dosing is NOT weight-based because venom load/delivery is not dependent on the victim's weight.

Please see the Figure 6 for a pit viper snake bite algorithm.

What are the adverse effects associated with each treatment option?

In 2001 Crotalidae Polyvalent Immune Fab became available for treating Crotalinae envenomations. Previously, Antivenin Crotalidae Polyvalent (ACP) (Wyeth Pharmaceuticals, Madison, NJ) was the only commercially available antivenom therapy. The two antivenoms differ in that FabAV is ovine-derived and consists predominantly of Fab fragments. ACP was equine-based and consisted of whole immunglobulin G. Thus, possible adverse reactions include acute reactions such as pruritis, rash, or urticaria in addition to true anaphylaxis. The incidence of such reactions has significantly decreased with the use of CroFab compared with ACP, and occurs in 5-6% of patients.

Serum sickness may occur as a result of receiving antivenom. Again, the incidence has significantly decreased since the use of CroFab and is seen in less than 20% of patients. Recurrence of local injury or systemic effects (coagulopathy) after initial resolution was an observation during clinical trials for CroFab; thus, the maintenance dosing schedule described above (two vials every 6 hours for three doses) was created and tested in the second trial. Of note, recurrent coagulopathy can still present despite maintenance dosing and may require additional vials of antivenom. Thus, patients should be advised to seek medical attention for persistent pain or new onset bruising or bleeding during the one to two weeks following treatment. In addition, repeat assessment of coagulation studies during this time is highly advised.

Relative contraindications to the use of FabAV include patient allergy to papaya, papain, or to FabAV.

In addition to the potential side effects described above, other risks include the theoretic risk of volume overload in children less than 10 kg.

FabAV is stabilized with the preservative thimerosal; this may be a concern for some families.

What are the possible outcomes of snake bite?

Appropriate treatment yields a very low incidence of death; annually there are about 5 deaths due to snake bite envenomation. In the last several years these have been Crotalinae envenomations in adults. Untreated envenomation can lead to death and/or disfigurement.

Increased compartment pressure can occur, likely secondary to myonecrosis. Envenomation often produces effects similar to those of true compartment syndrome such as pain, swelling, paresthesia, discoloration, and faint pulses. True compartment syndrome is rare. Additional antivenom and limb elevation are the recommended primary treatments for increased compartment pressure. If there is concern for compartment syndrome then compartment pressure should be monitored and an expert consultation obtained prior to consideration of surgical intervention.

What causes this disease and how frequent is it?

The latest comprehensive data on the incidence of snake bites in the United States was published in 1966 and reported approximately 45,000 snake bites annually, with 8,000 of those from venomous snakes. More recent data suggests approximately 6,000 snake bites annually reported and over 9,000 treated. Many feel this number is low due to underreporting. Approximately 5 fatalities occur annually.

Further, an assessment of national estimates of noncanine bite and sting injuries treated in US emergency departments from 2001-2010 revealed 9165 cases of snake bite with just over 30% attributed to venomous snakes.

Within the United States nearly every state has at least one venomous snake, with the exceptions of Hawaii, Alaska, and Maine. The majority of indigenous venomous snakes in the United States are of the family Viperidae and subfamily Crotalinae (rattlesnakes>, copperheads>, cottonmouths) and account for greater than 95% of the venomous snake bites. The other venomous snake is the coral snake of the Elapidae family.

A recent analysis by Seifert et al. of the American Association of Poison Control Center data for 2001-2005 related to venomous snake exposures found 30% of the victims were younger than 19 years of age and 12% were nine or younger. Florida, Texas, Arizona, California, North Carolina, Louisiana, and Georgia had the highest incidence of venomous snake bites during this time period. Coral snakes are predominantly found in Texas and Florida. Snake bites seasonally occur during April to October. Over 70% of the bites are to male victims.

Of note, a majority of snake bites are the result of intentional interaction and frequently involve alcohol.

How do these pathogens/genes/exposures cause the disease?

In general, snake venom composition can vary significantly from snake to snake and is dependent on a host of factors, some of which include snake age, geographic location, and diet.

Crotalinae (pit vipers) - The complex composition of the venom consists of varying proteins or enzymes that work to cause muscle necrosis, cell lysis, and/or increase cell permeability. Some components have direct hematological properties causing fibrinogen breakdown or even slowing fibrinogen function. Further, the Mojave toxin functions presynaptically and is associated with calcium channels. Pit viper venom may include such enzymes as phosphodiesterase, phospholipase, hyaluronidase or thrombin-like enzyme, to name a few.

Other clinical manifestations that might help with diagnosis and management

N/A

What complications might you expect from the disease or treatment of the disease?

N/A

Are additional laboratory studies available; even some that are not widely available?

An immunoassay exists for venom detection in Australia and Papua New Guinea for their most common five elapid venoms. An optical immunoassay was developed and tested in experimental envenomations for the four medically important snakes of South Vietnam.

How can snake bite be prevented?

Avoidance of any snake is key to preventing a snake bite envenomation. Snakes often strike when startled or threatened; thus, it is wise to recognize common places which they inhabit. For example, they may be found on cliff ledges, in tall grasses, dark holes, within wood piles, and swamps. When hiking or working outdoors, wear long pants and heavy boots and tread heavily. Lastly, consider using a flashlight at night to help avoid surprise encounters.

Ongoing controversies regarding etiology, diagnosis, treatment

Significant debate exists concerning fasciotomy. It is felt that the compartment-like syndrome associated with severe envenomations can be successfully treated with additional doses of antivenom. When compartment pressures are measured and monitored, the need and incidence of fasciotomy is rare. Insufficient evidence exists to suggest fasciotomy as a standard of practice.

Induced coagulopathy by snake bite envenomation is secondary to thrombin-like enzyme—not true thrombin—and thus is not inhibited by antithrombin III. Therefore, heparin is not recommended. Also, blood products provide additional substrate for Crotalinae venom and are not indicated except in cases of significant bleeding. The mainstay of treatment for coagulopathy is additional antivenom.